The hallmark of the immune response is specificity and memory which depend upon a variety of cellular and humoral interactions among immune cells and cytokines. A better understanding of the most basic elements of the immune response is necessary in order modify effectively immune response as they relate to cancer. Thus, the overall goal of the Program Project is to dissect the multiple closely interrelated factors that determine immune responses to conventional and tumor antigens. The program consists of six complementary projects: Dr. Fitch plans to define the complex interactions of lymphokines and cytokines that regulate the cellular immune response. Particular attention will be given to identifying molecular events and cell surface structures responsible for the differential activation of T(H)l and T(H)2 cells. Dr. Sant will study the critical sites in MHC class II molecules which determine the intracellular association and trafficking of class II molecules for presentation of soluble and endogenous antigens. She will also examine the nature of cell- and lineage-specific effects on antigen presentation. Dr. Quintans will analyze the ability of T cells to regulate other T cell responses. He proposes to study the mechanism for the accessory call function of T(H)2 cells and to analyze the possible role of class II and Fc receptor expression on this T cell subset in regulating immune responses to soluble antigens and tumors. Dr. Bluestone's project focusses on the use of monoclonal antibodies and other T cell receptor-specific reagents such as staphylococcal enterotoxins to potentiate viral and tumor immunity. Dr. Singh will study gene expression in T cell development and T call activation during immune responses. His studies will focus on one developmentally regulated gene, Oct-2, which is shown to be important in B cell development and expressed in T cells. Dr. Schreiber proposes to define the mechanisms .whereby heritable progressor variants of regressor tumors escape in the normal host while retaining CTL-defined target antigens. He will study differences in gene expression between regressor and progressor variants and analyze the possible role of distinct T call subsets and lymphokine production in tumor progression. Together, these six projects-will provide essential knowledge on critical interrelated mechanisms by which T calls, antigens-presenting cells, lymphokines and tumor antigen interact to regulate immune responses including those to cancer.